Mechanism for a Drug Delivery Device and Drug Delivery Device Comprising the Mechanism

ABSTRACT

The mechanism comprises a body, a drive member movable in the body, a main spring that is loaded when a dose is set and is released for moving the drive member during a delivery of a dose, and a movable trigger inhibiting a movement of the drive member, a movement of the trigger releasing the main spring and the drive member. The trigger is moved from a start position to an end position relative to the body during a setting of a dose, the end position having a distance from the start position that increases as the dose set increases.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a U.S. National Phase Application pursuant to35 U.S.C. §371 of International Application No. PCT/EP2014/068645 filedSep. 3, 2014, which claims priority to European Patent Application No.13182748.7 filed Sep. 3, 2013. The entire disclosure contents of theseapplications are herewith incorporated by reference into the presentapplication.

FIELD OF INVENTION

This invention relates to a mechanism for use in a drug delivery devicethat can be operated to deliver a number of user variable doses ofmedicament.

BACKGROUND

EP 1 819 382 B1 describes an injection device comprising a housing, adose setting member, a torsion spring connected to the dose settingmember in such a way that energy is accumulated in the torsion springupon rotation of the dose setting member, and a rotatably mounteddisplay member, which is threadedly engaged with the housing, coupledwith the dose setting member and provided to display the dose set. Adrive member is coupled with the dose setting member via aunidirectional ratchet. Upon release of a locking member, the torsionspring rotates the drive member, and the drive member rotates a pistonrod, which is helically advanced by a threaded engagement with thehousing. The dose setting member is axially retractable, and the doseset can be reset or reduced when the dose setting member is pulled todisengage the ratchet.

WO 2010/020311 A1 describes an injection device comprising a housingwith a first window provided with a first lens, and an inner sleeve witha second window provided with a second lens, which slides axially withinthe first window to display numbers indicating the size of a selecteddose. The numbers are helically arranged on an axially locked rotatabledial sleeve, which is arranged inside the inner sleeve and is threadedlyengaged with the inner sleeve. The rotation of the dial sleeve issynchronized with the displacement of the second window. The lens in thefirst window distorts the display, and the lens in the second windowcompensates for the distortion to increase the legibility of the numberviewed through both windows.

SUMMARY

It is an object of the present invention to provide a new mechanism fora drug delivery device that facilitates the use. It is a further objectto provide a new drug delivery device that facilitates the use.

These objects are achieved with the mechanism according to claim 1 andby the drug delivery device according to claim 12. Embodiments derivefrom the respective dependent claims.

In one aspect the invention relates to a mechanism for a drug deliverydevice. The mechanism comprises a body, a drive member, which is movablein the body and may be provided to drive an element like a lead screw ora piston rod, a main resilient element like a main spring that is loadedwhen a dose of a drug to be delivered is set by a user and is releasedfor moving the drive member during a delivery of a dose of a drug by auser, and a movable trigger inhibiting a movement of the drive member, amovement of the trigger with respect to the body releasing the mainresilient element and the drive member. The trigger is moved from astart position to an end position relative to the body during a settingof a dose, the end position having a distance, particularly a lineardistance, from the start position that increases as the dose setincreases.

The movable trigger facilitates the preparation of the mechanism for thedelivery of a dose of a drug and provides an optical and/or tactilefeedback of the amount of the drug set. The trigger may be provided byany operation element that can be moved from a start position to an endposition.

In an embodiment of the mechanism the trigger is moved from the endposition towards the start position for a delivery of a dose.

The use of the trigger facilitates the delivery of the dose set andprovides an optical and/or tactile feedback of the amount of the drug tobe delivered. The delivery is stopped when the movement of the triggeris stopped before its start position is reached. This mechanism thusallows a closer control of the delivery by the user than a conventionalmechanism.

In a further embodiment of the mechanism the end position of the triggerhas a distance from the start position that depends on the amount of thedose set. The dependence enhances the optical and/or tactile feedback ofthe amount of the drug set.

In a further embodiment of the mechanism the distance covered by thetrigger comprises a portion that is proportional to the dose delivered.The proportionality enhances the optical and/or tactile feedback of theamount of the drug to be delivered.

In a further embodiment of the mechanism the body defines an axialdirection, and the trigger is axially movable with respect to the bodyand is rotationally locked to the body, so that the position of thetrigger with respect to the body can change in the axial direction butthe trigger is not rotated with respect to the body.

The movement of the trigger in the axial direction without rotationenhances the optical and/or tactile feedback of the amount of the drugset and the optical and/or tactile feedback of the amount of the drugthat has already been delivered and of the amount of the drug thatremains to be delivered, respectively.

In a further embodiment the mechanism further comprises a lockingfeature releasably locking the drive member to the trigger, the lockingfeature being released for drug delivery.

The releasable lock allows the drive member to be locked to the triggerfor dose setting and to be released for drug delivery.

In a further embodiment of the mechanism the locking featurerotationally locks the drive member to the trigger, so that no relativerotation between the drive member and the trigger is possible.

The rotational lock prevents a rotation of the drive member during dosesetting, so that no unintended movement of the lead screw or piston rodis generated.

In a further embodiment of the mechanism the locking feature comprises aspline of the trigger, and a spline of the drive member, the splinesrotationally locking the drive member to the trigger in such a way thatthe rotational locking is released by a movement of the trigger from theend position towards the start position.

The splines provide a rotational locking that is easily engaged anddisengaged.

In a further embodiment the mechanism further comprises a trigger springacting on the trigger, the trigger spring tending to keep the drivemember locked to the trigger.

The trigger spring tends to keep the locking features engaged and iseasily compressed to allow the locking features to be disengaged.

In a further embodiment the mechanism further comprises an indicatormember, the drive member being unidirectionally rotationally coupled tothe indicator member.

The indicator member allows the dose set and/or delivered to beindicated according to the movement of the drive member.

In a further embodiment the mechanism further comprises a resilientelement acting between the body and the drive member, the resilientelement being arranged to keep the drive member coupled to the indicatormember.

The resilient element allows the coupling between the drive member andthe indicator member to be removed when the dose set is cancelled.

In a further embodiment the mechanism further comprises a spring capaxially movable and rotationally locked to the body, the main resilientelement being fastened to the indicator member and to the spring cap insuch a manner that the main resilient element is loaded by a rotation ofthe indicator member relative to the spring cap.

The spring cap allows the proximal interface of the main resilientelement to move axially with respect to the body, so that the mainresilient element is free to move axially with respect to the body asits distal interface with the indicator member moves axially when a doseis set.

In a further embodiment the mechanism comprises a body defining aproximal and a distal direction, a rotatable dial extending from thebody in the proximal direction, a lead screw, which is threadedlyengaged with the body and may be used to advance a bung in a drugcartridge, an indicator member, particularly for indicating an amount ofa drug, coupled with the dial, a main spring that is loaded by arotation of the indicator member relative to the body, a drive memberrotationally locked to the lead screw, and a trigger, which rotationallylocks the drive member to the body in such a way that the rotationallocking can be released. The indicator member is threadedly engaged withthe lead screw. An intermediate sleeve, which is used for transmission,is rotationally locked to the indicator member. A dial nut isrotationally locked to the dial and engages the intermediate sleeve in aunidirectional rotational gear or ratchet, thus coupling the indicatormember with the dial. The drive member is unidirectionally rotationallycoupled to the indicator member. The trigger is axially movable androtationally locked to the body. The rotational locking of the drivemember to the body is released by moving the trigger in the distaldirection in correspondence with a distal movement of the drive memberthat accompanies a distal movement of the lead screw. Rotation of thedrive member is required to generate a distal movement of the leadscrew.

The dial is used for setting and cancelling a dose of a drug and rotatesthe indicator member, which is coupled with the drive member via thedial nut and the intermediate sleeve in such a manner that a set dosecan be cancelled by rotating the dial back. The cancellation step makesuse of the unidirectional gears or ratchets. The indicator member ismoved according to the threaded engagement with the lead screw, which isstationary during dose setting. The trigger is used to release energythat is stored in the main spring.

In an embodiment of the mechanism the rotational locking of the drivemember to the body is released for drug delivery, and an axial distancecovered by the movement of the trigger during drug delivery increases asa dose of the drug delivered increases. The axial distance covered bythe movement of the trigger during drug delivery may especially beproportional to the dose of the drug delivered.

The use of the trigger allows a control during the delivery of the doseset and provides an optical and/or tactile feedback of the amount of thedrug that has already been delivered and of the amount of the drug thatremains to be delivered.

In a further embodiment the mechanism further comprises a resilientelement between the body and the drive member, the resilient elementacting on the drive member in the proximal direction.

The resilient element generates a coupling between the drive member andthe indicator member.

In a further embodiment of the mechanism the indicator member isarranged in the proximal direction relative to the drive member, and theresilient element acts on the drive member to keep the drive membercoupled to the indicator member.

The resilient element allows the coupling between the drive member andthe indicator member to be removed when the dose set is cancelled.

In a further embodiment the mechanism further comprises ratchet featuresunidirectionally rotationally coupling the drive member to the indicatormember.

The ratchet features allow the set dose to be cancelled withoutadvancing the lead screw.

In a further embodiment of the mechanism the intermediate sleeve axiallycontacts the drive member, so that the unidirectional rotationalcoupling between the indicator member and the drive member can bereleased by a movement of the intermediate sleeve in the distaldirection.

This is useful for cancelling a dose set.

In a further embodiment of the mechanism the movement of theintermediate sleeve in the distal direction is generated by a rotationof the dial nut relative to the intermediate sleeve, the rotation of thedial nut disengaging the gear or ratchet and pushing the intermediatesleeve in the distal direction.

The disengagement can thus be effected by a rotation of the dial via thedial nut.

In a further embodiment the mechanism further comprises a spline of thetrigger and a spline of the drive member, the splines rotationallylocking the drive member to the trigger in such a way that therotational locking can be released. A trigger spring acts on the triggerin the proximal direction to keep the drive member rotationally lockedto the trigger.

The splines provide a rotational locking that is easily engaged anddisengaged.

In a further embodiment of the mechanism the dial is axially constrainedto the body. If the dial is kept at the same axial position with respectto the body, the operation of the device may be facilitated.

In a further embodiment the mechanism further comprises a spring capaxially movable and rotationally locked to the body. The main spring isfastened to the indicator member and to the spring cap in such a mannerthat the main spring is loaded by a rotation of the indicator memberrelative to the spring cap.

The spring cap allows the main spring to move axially with respect tothe body.

In a further embodiment of the mechanism the main spring is a torsionspring, and the spring cap moves in the distal direction when theindicator member moves in the distal direction and vice versa.

The spring cap allows the main spring to move simultaneously with theindicator member.

In a further aspect the invention relates to a drug delivery devicecomprising a mechanism as recited above. In particular the drug deliverydevice may be a pen-type device and/or a disposable device, which is notrefilled when it is empty. The drug delivery device may especially be aninjection device, in particular a pen-type injector.

The term “drug”, as used herein, preferably means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exendin-3 or exendin-4 or an analogue or derivative ofexendin-3 or exendin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 Exendin-4(1-39),

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-H2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150 kDahttp://en.wikipedia.org/wiki/Dalton_%28unit%29) that are also known asimmunoglobulins which share a basic structure. As they have sugar chainsadded to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and 6 approximately 500 amino acids, whileμ and ε have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (C_(H)) and the variable region (V_(H)). Inone species, the constant region is essentially identical in allantibodies of the same isotype, but differs in antibodies of differentisotypes. Heavy chains γ, α and δ have a constant region composed ofthree tandem Ig domains, and a hinge region for added flexibility; heavychains μ and ε have a constant region composed of four immunoglobulindomains. The variable region of the heavy chain differs in antibodiesproduced by different B cells, but is the same for all antibodiesproduced by a single B cell or B cell clone. The variable region of eachheavy chain is approximately 110 amino acids long and is composed of asingle Ig domain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H—H interchaindisulfide bond. F(ab′)2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

BRIEF DESCRIPTION OF THE DRAWINGS

The following is a detailed description of embodiments of the mechanismand drug delivery device in conjunction with the appended drawings.

FIG. 1 is a cutaway view of a pen-type injector.

FIG. 2 shows a cross section of an embodiment of the mechanism.

FIG. 3 shows a lead screw comprising a thread, an axial groove and abearing.

FIG. 4 is a cutaway view of a middle section of the embodiment accordingto FIG. 2.

FIG. 5 is a cutaway view of a proximal section of the embodimentaccording to FIG. 2.

FIG. 6 shows a schematic cross section of the middle section of theembodiment according to FIG. 2.

FIG. 7 is a cutaway view of a distal part of the mechanism.

FIG. 8 is a cutaway view of coupled elements of the mechanism.

FIG. 9 is a further cutaway view of the part of the mechanism shown inFIGS. 7 and 8.

FIG. 10 is a cutaway view showing the arrangement of threads on elementsof the mechanism.

FIG. 11 shows semitransparent views of the proximal part of a drugdelivery device in different states during dose dialing.

FIG. 12 is a further cutaway view of the part of the mechanism accordingto FIG. 7 for another state of the mechanism.

FIG. 13 is the cutaway view of FIG. 12 for still another state of themechanism.

FIG. 14 shows an example of a display of the drug delivery device.

FIG. 15 shows a further example of the display.

FIG. 16 shows still a further example of the display.

FIG. 17 is a further cutaway view of the middle section of theembodiment according to FIG. 4 including additional details.

FIG. 18 is a semitransparent view of a proximal section of an embodimentof the mechanism.

FIG. 19 is a semitransparent view of the proximal section of theembodiment according to FIG. 11 including details from FIGS. 17 and 18for the state of the mechanism before dialing.

FIG. 20 shows a cross section of the proximal section according to FIG.19.

FIG. 21 is a semitransparent view according to FIG. 19 for the state ofthe mechanism after dialing.

FIG. 22 shows a cross section according to FIG. 20 for the state of themechanism according to FIG. 21.

FIG. 23 is a further cutaway view of the middle section of theembodiment of the mechanism including details from FIGS. 4 and 17.

FIG. 24 is a cutaway view according to FIG. 23 for the state of themechanism after dialing the final dose.

FIG. 25 shows further cutaway views according to FIG. 9 for a state ofthe mechanism at the start of a cancellation of the dose set.

FIG. 26 shows further cutaway views according to FIG. 25 for a state ofthe mechanism during the cancellation of the dose set.

FIG. 27 shows further cutaway views according to FIG. 25 for a state ofthe mechanism at the end of a step for cancelling the dose set.

FIG. 28 is a semitransparent view according to FIG. 21 for a state ofthe mechanism after setting and before dispensing a dose.

FIG. 29 is a cross section according to FIG. 22 for the state of themechanism according to FIG. 28.

FIG. 30 is a semitransparent view according to FIG. 28 for a state ofthe mechanism after dispensing half of the dose set.

FIG. 31 is a cross section according to FIG. 29 for the state of themechanism according to FIG. 30.

FIG. 32 is a semitransparent view according to FIG. 28 for a state ofthe mechanism after dose dispense.

FIG. 33 is a cross section according to FIG. 29 for the state of themechanism according to FIG. 32.

DETAILED DESCRIPTION

FIG. 1 is a cutaway view of a pen-type injector comprising an embodimentof the mechanism. The pen-type injector is shown as an example of thedrug delivery device, and the mechanism is also suitable for other typesof drug delivery devices. The pen-type drug delivery device comprises areceptacle for a drug like a medicament cartridge 1 placed in acartridge holder 2, which may be provided to facilitate the assemblingof the device. A trigger 3 is provided for the operation of themechanism and enables the delivery of a dialed dose of the drug by meansof a bung 5. A display may include a fixed window 4, which is formed inthe body 6 of the device. A receptacle for the drug or a compartment fora cartridge can be formed by the body 6. If a cartridge holder 2 isused, it is fastened to the distal end of the body 6. The body 6 may beformed as a unity or may comprise an external housing and one or moreinserted parts. A dial 7 is provided for the operation of the mechanismand is used to dial a dose of the drug. The rotation of the dial 7 isindicated in FIG. 1 by curved arrows. The mechanism will be describedfor an embodiment in which a clockwise rotation of the dial 7, as viewedin the distal direction, increases the dialed dose and acounter-clockwise rotation of the dial 7 decreases the dialed dose andmay particularly cancel the dose completely. In other embodiments theoperation of the dial 7 may be reversed, depending on how the elementsof the mechanism are coupled.

The body 6 and the entire drug delivery device comprising the body 6have a distal end and a proximal end. The term “distal end” designatesthat end of the body, the device or a component thereof which is or isto be arranged closest to a dispensing end of the drug delivery device.The term “proximal end” designates that end of the body, the device or acomponent thereof which is or is to be arranged furthest away from thedispensing end of the drug delivery device. The term “distal direction”means the direction from the proximal end towards the distal end. Theterm “proximal direction” means the direction from the distal endtowards the proximal end. In FIG. 1 these directions are indicated bystraight arrows, which also indicate the axial directions with respectto the body 6 and furthermore define an axis of the body 6. The terms“axial movement” and “translation” will be used to describe a movementof an element of the mechanism relative to the body 6 in the axialdirection, and this movement may or may not include a rotation aroundthe axis. The terms “rotation” and “rotational” will be used to describea movement of an element of the mechanism relative to the body 6 aroundthe axis.

FIG. 2 shows a cross section of an embodiment of the mechanism, arrangedin a pen-type drug delivery device, according to the device shown inFIG. 1. Elements that correspond to elements of FIG. 1 are designatedwith the same reference numerals in FIG. 2. Additionally to the fixedwindow 4, the bung 5, the body 6 and the dial 7, FIG. 2 shows a leadscrew 9 with an optional bearing 8 arranged between the bung 5 and thelead screw 9, a resilient element 10, which may be a helical spring, forinstance, an indicator member in the shape of a number sleeve 11, amovable window, which may especially be a sliding window 12, and whichmay be provided as a part of the display, a main spring 13, a triggerspring 14, which may be a helical spring, for instance, a drive member,which may have any suitable shape like a nut, a ring or a sleeve, forinstance, and will be designated as drive disc 15 in the followingdescription, an intermediate sleeve 16 provided as a coupling element, adial nut 17, and a spring cap 18 provided for the main spring 13. Thearrangement and function of these parts will become apparent from thefollowing detailed description.

FIG. 3 shows the lead screw 9 with the bearing 8. The distal end of thelead screw 9 connects to the bearing 8 to permit a relative rotation butprevent an axial separation of the bearing 8 and the lead screw 9. Thedistal face of the bearing 8 abuts the bung 5 in order to facilitate thetransmission of a helical movement of the lead screw 9 to a translationof the bung 5, which expels the drug in the distal direction. Thepresence of a bearing 8 is preferred but it is optional. The lead screw9 comprises a screw thread 19, which is left-handed in the example shownin FIG. 3, but may instead be right-handed. The differences derivingfrom the different types of the screw thread 19, which yield essentiallysimilar mechanisms, will become apparent from the following description.The lead screw 9 is provided with a structure that allows a furtherelement to slide axially along the lead screw 9 and rotationally locksthe further element relative to the lead screw 9. This structure maycomprise a plurality of splines arranged in a line and/or a groove 20,which intersects the screw thread 19 without inhibiting a threadedengagement with a further element. The described embodiment comprises apair of straight grooves 20 arranged opposite to one another parallel tothe axis of the lead screw 9. A further structure may be provided nearthe proximal end of the lead screw 9 to form a last-dose abutment 21 ofthe lead screw 9. The function of the last-dose abutment 21 will bedescribed below.

FIG. 4 is a cutaway view of a middle section of the embodiment accordingto FIG. 2 with the trigger 3 and the trigger spring 14 removed. FIG. 4shows how the lead screw 9 can be rotationally locked to the drive disc15 by means of the groove 20 engaging a spline or protrusion of thedrive disc 15. Splines of the lead screw 9 may instead engage grooves ofthe drive disc 15. The lead screw 9 and the drive disc 15 are coupled insuch a manner that they are only able to rotate simultaneously, whereasan axial movement of the lead screw 9 relative to the drive disc 15 ispossible. A threaded body web 22 is provided to guide a helical movementof the lead screw 9 relative to the body 6. The helical movement isleft-handed if the thread 19 of the lead screw 9 is left-handed. In thiscase a counterclockwise rotation of the drive disc 15, viewed in thedistal direction, causes the lead screw 9 to advance helically in thedistal direction. If the lead screw 9 is instead provided with aright-handed thread 19, a clockwise rotation of the drive disc 15 makesthe lead screw 9 advance in the distal direction. The threaded body web22 is particularly suitable, but a threaded engagement between the body6 and the lead screw 9 can instead be effected by another part orcomponent of the body 6. FIG. 4 further shows a first thread 34 of thenumber sleeve 11, which is thereby threadedly engaged with the leadscrew 9. The first thread 34 may be formed in a central bore of a distalflange 50 of the number sleeve 11, for example.

FIG. 5 is a cutaway view of a proximal section of the embodimentaccording to FIG. 2. The dial 7 comprises an axial constraint 23, asleeve 24 inside the body 6 and a button 25 outside the body 6, whileother shapes of the dial 7 may be suitable as well. The axial constraint23 is provided to allow a free rotation of the dial 7 and to prevent atranslation, thus axially constraining the dial 7 to the body 6. Theaxial constraint 23 may be formed by a cylindrical extension of the dial7 with a beaded rim, which is inserted in a chamfer or furrow of thebody 6, for example, as shown in FIG. 5. The dial 7 may thus be turnedwithout being separated from the body 6. The rotation is transferred tothe dial nut 17, which is rotationally locked, in particular splined,for example, to the sleeve 24 of the dial 7. An axial movement of thedial nut 17 is allowed within a limited range, as will be describedbelow. The user of the device rotates the dial 7 by means of the button25 to set and unset a dose. In the described embodiment a clockwiserotation of the dial 7 increases the dose set whereas a counterclockwiserotation decreases the dose set.

FIG. 6 shows a schematic cross section of the middle section of thedescribed embodiment of the mechanism. FIG. 6 shows the relativepositions of the lead screw 9, the number sleeve 11, the drive disc 15,the intermediate sleeve 16, and the dial nut 17, which is axiallyconstrained in the proximal direction (to the right in the arrangementshown in FIG. 6) by abutments 26 on an inner surface of the numbersleeve 11. The abutments 26 may engage with radial bosses 51 of the dialnut 17, for example. The radial bosses 51 also rotationally link thedial nut 17 to the intermediate sleeve 16 and are profiled to transfer atorque to the intermediate sleeve 16 during setting of a dose and totransfer both a torque and an axial force to the intermediate sleeve 16during a cancellation of the dose set. The intermediate sleeve 16 thusobtains the function of a reversing sleeve.

FIG. 7 is a cutaway view of a distal part of the mechanism. The crosssection face 29 is not an actual surface of the body 6 but represents animaginary plane that is formed by the cross section only. Ratchetfeatures, which may be ratchet teeth 27, on the distal face of thenumber sleeve 11 engage with corresponding features on the drive disc15. Each of the ratchet teeth 27 has preferably two engaging surfaces,which extend essentially radially with respect to the axis of the body6, are ramped in opposite azimuthal directions and have differentslopes. When the ratchet teeth 27 are engaged, corresponding surfaces ofthe ratchet teeth 27 are in contact. The different slopes cause aunidirectional rotational coupling between the number sleeve 11 and thedrive disc 15, which are rotationally locked in one sense of rotation,while the ratchet can be overridden in the opposite sense of rotation.In the described embodiment, the number sleeve 11 and the drive disc 15are rotationally locked when the number sleeve 11 is rotatedcounterclockwise with respect to the distal direction. The resilientelement 10 acts between the body 6 and the drive disc 15 and applies anaxial force on the drive disc 15 in the proximal direction to maintainthe engagement of the ratchet features. The resilient element 10 may bea helical spring which is supported by an inner body face 28, which maybe a proximal surface of the threaded body web 22, for example.

FIG. 8 is a cutaway view of coupled elements of the mechanism. Theintermediate sleeve 16 is splined to the number sleeve 11. This can beachieved by a spline engagement 31 of an axial boss 32 protrudingthrough the distal flange 50 of the number sleeve 11. The axial boss 32abuts the drive disc 15 and is thus in a position to push the drive disc15 axially in the distal direction. There may be any number of suchaxial bosses 32, of which there are four in the described embodiment.FIG. 8 also clearly shows how the first thread 34 of the number sleeve11, which is provided for a threaded engagement with the lead screw 9,may be formed in the central bore of the distal flange 50 of the numbersleeve 11.

FIG. 9 is a further cutaway view of the part of the mechanism shown inFIGS. 7 and 8 with the number sleeve 11 removed, and further explainsthe interaction of the dial nut 17 with the intermediate sleeve 16 bymeans of contact faces 33, 33′ of different inclinations, which form afurther unidirectional rotational gear or ratchet. The curved arrow inFIG. 9 indicates the clockwise rotation of the dial 7 during dosesetting. The torque is transferred from the dial 7 via the splinedengagement with the dial nut 17 to the intermediate sleeve 16 by thosecontact surfaces 33 that have a steep slope. The number sleeve 11 issimultaneously rotated because of the splined engagement of theintermediate sleeve 16, which may be achieved with axial bosses 32 ofthe intermediate sleeve 16 engaging recesses of the distal flange 50 ofthe number sleeve 11, as described above. As the number sleeve 11 isthreadedly engaged with the lead screw 9 by the first thread 34, arotation of the number sleeve 11 generates a translation of the numbersleeve 11 when the lead screw 9 is kept rotationally locked relative tothe body 6, as will be described below.

FIG. 10 is a cutaway view showing the arrangement of threads on elementsof the mechanism. The number sleeve 11 is threaded to the lead screw 9by the first thread 34 and to the sliding window 12, which is a part ofa window arrangement, by a second thread 35. The fixed window 4 and thesliding window 12 form the window arrangement, and the sliding window 12is movable within dimensions of the fixed window 4. As the design of thesliding window 12 limits its movements to translations within thedimensions of the fixed window 4, a rotation of the number sleeve 11generates an axial movement of the sliding window 12. As a result of thevarious engagements described above a clockwise rotation of the sleeve24 of the dial 7 generates simultaneous clockwise rotations of the dialnut 17, the intermediate sleeve 16 and the number sleeve 11, and theleft-handed first thread 34 makes the number sleeve 11 move in theproximal direction, as long as the lead screw 9 stays stationary withrespect to the body 6. Accordingly a counterclockwise rotation of thesleeve 24 of the dial 7 generates simultaneous counterclockwiserotations of the dial nut 17, the intermediate sleeve 16 and the numbersleeve 11, and the left-handed first thread 34 makes the number sleeve11 move in the distal direction. The second thread 35 is alsoleft-handed if the first thread 34 is left-handed and is right-handed ifthe first thread 34 is right-handed. In any case an axial movement ofthe number sleeve 11 in the proximal direction generates an axialmovement of the sliding window 12 in the distal direction and viceversa. The range of the movement of the sliding window 12 relative tothe number sleeve 11 is thus considerably larger than the distancescovered by either element with respect to the body 6. This facilitatesthe implementation of this type of display in a compact device.

FIG. 11 shows semitransparent views of the proximal part of a drugdelivery device in different states during dose dialing. FIG. 11A showsthe state with no dose yet dialed and the sliding window 12 at its mostproximal position. When the button 25 of the dial 7 is turned clockwise,according to the curved arrow, the sliding window 12 starts to move inthe distal direction, as indicated by the upper straight arrow, and thenumber sleeve 11 starts to move in the proximal direction, as indicatedby the lower straight arrow. FIG. 11B shows the state with the dosepartially dialed and the sliding window 12 passed halfway through thefixed window 4. It can be seen that the engagement between the numbersleeve 11 and the drive disc 15 is maintained by means of the resilientelement 10. FIG. 11C shows the state with a maximal dose dialed and thesliding window 12 at its most distal position. The resilient element 10is maximally extended, but the engagement between the number sleeve 11and the drive disc 15 is still maintained.

FIG. 12 is a further cutaway view of the part of the mechanism accordingto FIG. 7 for the state of the mechanism in which no dose is set. Anend-of-dose stop 36 may be provided by a radially extending abutmentfeature on the number sleeve 11. The abutment feature is provided toengage with a spline or a similar feature of the body 6 to prevent acancelling rotation, which is counter-clockwise in the describedembodiment, when no dose is dialed or cancelling is completed. Theabutment feature is shown in FIG. 12 as a radial protrusion withclockwise decreasing radius around the rim of the number sleeve 11. Itsouter surface thus forms a spiralling circumference with a stop forcounter-clockwise rotation and a ramp for clockwise rotation, whichenables the corresponding abutment feature of the body 6 to beoverridden when dialing starts and the number sleeve 11 may not yet havemoved sufficiently far in the proximal direction to separate thecorrespondent abutment features axially.

The dose to be dispensed can be displayed on the number sleeve 11through the fixed window 4 and the sliding window 12. To this end thesliding window 12 displays a surface area of the number sleeve 11, whichmay be provided with a helical path of numbers 38, the pitch of thehelix matching the pitch of the second thread 35 of the number sleeve 11coupling the number sleeve 11 and the sliding window 12. The path ofnumbers may be printed directly on the number sleeve 11, for instance,or it may be provided by a printed sheet or foil, which is wrappedaround the number sleeve 11.

FIG. 13 is a further cutaway view of the part of the mechanism accordingto FIG. 7 for the state of the mechanism in which a maximal dose is set.A maximum-dose stop 37 may be provided by a further radially extendingabutment feature on the number sleeve 11. When a maximal dose has beendialed, the further abutment feature stops the rotation of the numbersleeve 11 by abutting the sliding window 12, which approaches the distalend of the fixed window 4 in this state of dialing.

The number 38 on the number sleeve 11 indicating the dose set ispreferably displayed through the sliding window 12. Even if the fixedwindow 4 stays open in its entirety, the display can be confined to thearea of the sliding window 12. This may be achieved by using atransparent cover of the fixed window 4 that is profiled to distort thelight path sufficiently to make the numbers on the number sleeve 11illegible when viewed through the fixed window 4 alone. The slidingwindow 12 is designed to correct the optical distortion caused by thefixed window 4 to ensure that the number 38 corresponding to the doseset is legible, while the other numbers, which are not in the area ofthe sliding window 12, remain illegible. The sliding window 12 mayalternatively or additionally provide a magnifying effect to increasethe character size of the display.

FIG. 14 shows an example of such a display of the drug delivery device.The arrangement of the display including the fixed window 4 and thesliding window 12 is shown in FIG. 14A. The numbers of the number sleeve11 are visible in the open fixed window 4, but only the number in thebordered frame of the sliding window 12 is easily legible. This isachieved by a distorting surface structure of the transparent cover ofthe fixed window 4 that is optically compensated by the sliding window12, which is preferably provided with the complementary surfacestructure. FIG. 14B shows an embodiment in which the surface structureforms a waved surface comprising a plurality of parallel ridges 39, forinstance, with curved valleys in between. The surface of the slidingwindow 12 that faces the structured surface of the fixed window 4 isprovided with corresponding ridges, which are arranged between theridges 39 of the fixed window 4 and form a complementary waved surface.The ridges 39 are arranged in the axial direction to allow the slidingwindow 12 to move over the fixed window 4 with the corresponding wavedsurfaces touching one another. The number and form of the ridges 39 areadapted to obtain the desired optical effect. FIG. 14C shows a furtherembodiment of a transparent cover of the fixed window 4 in a crosssection transverse to the axial direction. In this example the ridges 39are smoothly curved while the valleys in between are not. Thecomplementary surface of the sliding window 12 comprises smoothly curvedgrooves between sharp ridges. The curved ridges may instead be formed onthe sliding window 12 and the corresponding grooves and sharp ridges onthe transparent cover of the fixed window 4. The examples show that anyoptically distorting shape of the surface structure may be suitable thatallows the sliding window 12 to move axially relative to the fixedwindow 4.

FIG. 15 shows a further example of the display. In this embodiment thetransparent cover of the fixed window 4 forms a distorting lens 40having a V-shaped cross section transverse to the axial direction. Thedistorting lens 40 distorts the numbers outside the area of the slidingwindow 12, which has a complementary shape in order to compensate theoptical effect of the V-shaped distorting lens 40. Therefore the numberbehind the sliding window 12 is not distorted. FIG. 15C shows a furtherembodiment of a transparent cover of the fixed window 4 having a tripleV-shaped distorting lens 40 in a cross section transverse to the axialdirection. The examples show that any optically distorting lens 40 maybe suitable that allows the sliding window 12 to move axially relativeto the fixed window 4.

FIG. 16 shows still a further example of the display. In this embodimentthe transparent cover of the fixed window 4 forms a magnifying lens 41,which magnifies the numbers outside the area of the sliding window 12 inthe vertical direction. In order to compensate the optical effect of themagnifying lens 41 and to bring the number to be read back into focus,the sliding window 12 has a complementary shape, so that the numberbehind the sliding window 12 is not magnified and hence not distorted.FIG. 16C shows a further embodiment of a transparent cover of the fixedwindow 4 having a magnifying lens 41 in a cross section transverse tothe axial direction. The examples show that any optically distortingmagnifying lens 41 may be suitable that allows the sliding window 12 tomove axially relative to the fixed window 4.

FIG. 17 is a further cutaway view of the middle section of theembodiment according to FIG. 4 including additional details. The trigger3 is rotationally locked to the body 6 and is free to translate axiallybetween a distal stop feature 42 and a proximal stop feature 43. As longas the trigger mechanism is not operated by a user, splines 44 of thetrigger 3 engage with corresponding splines 45 of the drive disc 15,thus preventing a rotation of the drive disc 15 and the lead screw 9,which is rotationally locked with the drive disc 15. The splines 44, 45thus form a locking feature releasably, especially rotationally, lockingthe drive disc 15 to the trigger 3, the locking being released for drugdelivery, as will be described below. The trigger spring 14 acts betweenthe body 6 and the trigger 3 and applies an axial force in the proximaldirection to the distal face of the trigger 3 to maintain the engagementwith the drive disc 15. In the state shown in FIG. 17 the trigger 3 hasbeen moved distally, the trigger spring 14 is compressed, and thesplines 44, 45 are not engaged.

FIG. 18 is a semitransparent view of a proximal section of an embodimentof the mechanism. The main spring 13 is a torsion spring, which can beloaded by a rotation of the number sleeve 11. The ends of the mainspring 13 are fixed to the number sleeve 11 and to a spring cap 18,respectively. The distal fastening 46 of the main spring 13 to thenumber sleeve 11 and the proximal fastening 47 of the main spring 13 tothe spring cap 18 are shown in FIG. 18. The spring cap 18 isrotationally locked to the body 6 but is preferably free to move axiallywith the main spring 13. This may be achieved by grooves or splines 48that are arranged in the axial direction. The free translation of thespring cap 18 is preferred because it allows the axial extension of themain spring 13 to be essentially maintained, thus avoiding an additionalstrain that would be caused by a compression of the main spring 13during the intended torsional charging. Furthermore, the effectivetorque is larger when the loaded main spring 13 is released withoutbeing extended. This will become clear from the following description ofthe dose setting and delivery operations.

FIG. 18 also shows the sliding window 12, which is engaged with thenumber sleeve 11 by the second thread 35 of the number sleeve 11. Themain spring 13 is preferably pre-wound upon assembly, such that itapplies a torque to the number sleeve 11 when the mechanism is in theend-of-dose state. A rotation of the dial 7 to set a dose also rotatesthe dial nut 17, the intermediate sleeve 16 and the number sleeve 11,relative to the body 6 and the spring cap 18, and winds up the mainspring 13. The torque applied to the main spring 13 is reacted at theproximal end by the body 6 via the spring cap 18. At the distal end thetorque is reacted by the trigger 3, via the ratchet feature, especiallyratchet teeth 27, between the number sleeve 11 and the drive disc 15 andthe splines 44, 45 coupling the drive disc 15 to the trigger 3.

The setting of a dose will now be explained in conjunction with FIGS. 19to 22. FIG. 19 is a semitransparent view of the proximal section of theembodiment according to FIG. 11, including details from FIGS. 17 and 18,and FIG. 20 is a corresponding cross section. FIGS. 19 and 20 show theinitial state of the drug delivery device as delivered, ready to set thefirst dose, with the end-of-dose stop 36 still engaged. To set a dose,the dial 7 is rotated clockwise by means of the button 25, so that thenumber sleeve 11 is simultaneously rotated by means of further parts ofthe mechanism described above, as shown in the cross section of FIG. 20.The number sleeve 11 translates in the proximal direction because of itsthreaded engagement with the lead screw 9, which remains stationary. Asthe number sleeve 11 rotates, the second thread 35 causes the slidingwindow 12 to move across the helical path of numbers 38 in the distaldirection, so that the number 38 that is visible behind the slidingwindow 12 changes corresponding to the dose set. The ratchet teeth 27 atthe distal end of the number sleeve 11 ramp over the correspondingfeatures on the drive disc 15, creating tactile and audible feedback tothe user for each unit set. The ratchet features between the numbersleeve 11 and the drive disc 15 prevent the main spring 13 fromunwinding the number sleeve 11 when the dial 7 is released.

Both the drive disc 15 and the trigger 3 match the axial translation ofthe number sleeve 11 owing to the resilient element 10 and the triggerspring 14, which maintain the engagement of the ratchet teeth 27 betweenthe drive disc 15 and the number sleeve 11 and the engagement of thesplines 44, 45 coupling the drive disc 15 and the trigger 3. The triggerspring 14 acts on the trigger 3 in such a way that the trigger spring 14tends to keep the drive disc 15 locked to the trigger 3. The trigger 3is moved from a start position to an end position relative to the body 6during the setting of a dose, the end position having a distance fromthe start position that increases as the dose set increases. The endposition of the trigger 3 may especially have a distance from the startposition that is proportional to the dose set. As the dial 7 is rotatedrelative to the body 6 the main spring 13 is charged in torsion. Thespring cap 18 translates with the number sleeve 11, via the main spring13, in order to allow the main spring 13 to match the axial translationof the number sleeve 11.

FIG. 21 is a semitransparent view according to FIG. 19 for the state ofthe mechanism, in which the maximal dose is dialed and the maximum-dosestop 37 is engaged, and FIG. 22 is a corresponding cross section. Theuser may continue to dial up until the maximum-dose stop 37 is reached.During the dialing operation the trigger 3 and the drive disc 15translate axially, so that the splines 44 of the trigger 3 remainengaged with the splines 45 of the drive disc 15 until the dialing isstopped. The spring cap 18 is translated towards its proximal positionto prevent an overload of the main spring 13. When nearly all the dosesavailable in the drug delivery device have been delivered and the finaldose is dialed, the rotation of the dial 7 is stopped when the last-doseabutment 21 of the lead screw 9 engages the number sleeve 11, which mayoccur before the maximum-dose stop 37 is reached, as will be describedbelow.

FIGS. 23 and 24 are further cutaway views of the middle section of theembodiment of the mechanism including details from FIGS. 4 and 17, thetrigger 3 being omitted for clarity. FIGS. 23 and 24 explain theoperation of a last-dose feature. FIG. 23 shows the mechanism after anumber of doses have been delivered, with the device in the end-of-dosestate. The last-dose abutment 21 of the lead screw 9 is still at adistance from a corresponding last-dose abutment 49 of the number sleeve11. FIG. 24 shows a later state of the mechanism, when a dose has beendialed causing the number sleeve 11 to move helically towards theproximal end of the device, when the last-dose abutment 21 of the leadscrew 9 is in contact with the last-dose abutment 49 of the numbersleeve 11. Further dialing up of the mechanism is therefore prevented,as the lead screw 9 is rotationally locked, and contact of the last-doseabutment 21, 49 rotationally locks the number sleeve 11 in the clockwisedirection.

The cancellation of a set dose will now be described in conjunction withFIGS. 25 to 27, which show further cutaway views according to FIG. 9 fordifferent states of the mechanism during a dose cancelling operation. Aset dose can be cancelled by a rotation of the dial 7 in the oppositesense of the rotation during setting. In the described embodiment, thecancellation of a set dose involves a counterclockwise rotation of thedial 7, which rotates the dial nut 17 relative to the intermediatesleeve 16, which is rotationally locked to the body 6, because theintermediate sleeve 16 is rotationally locked to the number sleeve 11 bythe spline engagement 31, the number sleeve 11 is unidirectionallyrotationally locked to the drive disc 15 by the ratchet teeth 27, andthe drive disc 15 is rotationally locked to the body 6 via the trigger3. FIG. 25A shows the positions of the drive disc 15, the intermediatesleeve 16 and the dial nut 17, and FIG. 25B shows the arrangement of thedrive disc 15 and the number sleeve 11 during the counterclockwiserotation of the dial 7, indicated by the curved arrow. FIG. 26A showshow the dial nut 17 overrides the ramped contact faces 33′ of theunidirectional rotational gear by pushing the intermediate sleeve 16 inthe distal direction; the dial nut 17 is axially constrained in theproximal direction by the abutments 26 of the number sleeve 11, asexplained above in conjunction with FIG. 6. The axial bosses 32 of theintermediate sleeve 16 push the drive disc 15 out of its engagement withthe number sleeve 11, and the number sleeve 11 is free to rotatecounterclockwise, as shown in FIG. 26B. The rotation of the numbersleeve 11 is accelerated by the torque of the loaded main spring 13.This causes the intermediate sleeve 16, which is rotationally locked tothe number sleeve 11 by the spline engagement 31, to rotatecounterclockwise relative to the dial 7 and the dial nut 17, slidinghelically over the ramped contact faces 33′. This results in an axialmovement of the intermediate sleeve 16 back in the proximal direction,as shown in FIG. 27A, until the steep contact faces 33 are again incontact, and the ratchet features of the number sleeve 11 and drive disc15 are again engaged, as shown in FIG. 27B, by means of the resilientelement 10. The number sleeve 11 is now again prevented from rotatingcounterclockwise. As long as the dial 7 is rotated counterclockwise bythe user, the described process is repeated until the end-of-dosecondition is reached and the end-of-dose stop 36 engages.

The dose delivery will now be described in conjunction with FIGS. 28 to33. FIG. 28 is a semitransparent view of the mechanism at the start ofdispense, when the maximal dose is dialed and the sliding window 12displays the maximal number of units, which is 80 in this example. Themain spring 13 is loaded and the spring cap 18 is in its proximalposition near the button 25 of the dial 7. The arrangement of thetrigger 3, the drive disc 15, the number sleeve 11, the intermediatesleeve 16, the main spring 13, the spring cap 18 and the lead screw 9 isshown in FIG. 29. The trigger spring 14 is extended, but maintains thecoupling between the trigger 3 and the drive disc 15 by means of thesplines 44, 45.

The dose set is dispensed by translating the trigger 3 in the distaldirection with respect to the body 6, compressing the trigger spring 14,as shown in FIG. 28. This releases the splined engagement between thetrigger 3 and the drive disc 15, allowing the drive disc 15 to rotate,driven by the number sleeve 11, which is rotated by the loaded mainspring 13. The cross section of FIG. 29 shows how the rotating drivedisc 15 turns the lead screw 9 counterclockwise, because the drive disc15 is rotationally locked to the lead screw 9 by grooves or splines 20shown in FIG. 4. As the left-handed thread 19 of the lead screw 9 isguided by a thread of the body 6, especially by the threaded body web 22shown in FIG. 4, for instance, the lead screw 9 advances helically inthe distal direction and drives the bung 5, so that the dose set isexpelled from the receptacle, especially from the medicament cartridge1, for instance. The spring cap 18 translates in the distal direction,so that the main spring 13 is not extended, which would counteract therelease of the charged torsion.

Since the main spring 13 also acts on the number sleeve 11, the numbersleeve 11 rotates counterclockwise at the same rate as the drive disc15. The ratchet between the number sleeve 11 and the drive disc 15remains in engagement as these two parts translate with the lead screw9, maintaining the transmission of torque from the main spring 13.During the counterclockwise rotation of the number sleeve 11, thesliding window 12 is moving in the proximal direction and therebydisplays a sequence of numbers 38 indicating a decreasing amount of thedose remaining to be dispensed. The rotational locks that are providedin the mechanism cause the intermediate sleeve 16, the dial nut 17 andthe dial 7 to rotate counterclockwise together with the number sleeve 11during drug delivery.

FIG. 30 shows a semitransparent view of the mechanism according to FIG.28 for an intermediate state of the mechanism when about half the dosehas been dispensed. FIG. 31 shows a corresponding cross sectionaccording to FIG. 29. The sliding window 12 has moved halfway in theproximal direction and displays 40 units remaining to be dispensed. Thelead screw 9 has moved in the distal direction, and the distance betweenthe spring cap 18 and the button 25 has increased. Since the drive disc15 progressively translates during dispense, the user must continue toshift the trigger 3 to the distal end by further compressing the triggerspring 14, in order to keep the trigger 3 disengaged from the drive disc15. This provides clear tactile feedback that the dose is beingdispensed, while still requiring a low user force regardless of theforce required to move the bung 5. Releasing the trigger 3 at any timeduring dispense allows the trigger spring 14 to bias the splines 44 ofthe trigger 3 into engagement with the corresponding splines 45 of thedrive disc 15, preventing a further rotation of the drive disc 15, thenumber sleeve 11 and the lead screw 9, and ceasing dispense. Therotation of the drive disc 15 by the main spring 13 continues until thenumber sleeve 11 contacts the end-of-dose stop 36 or the user releasesthe trigger 3. The trigger 3 is moved from the end position towards thestart position during the delivery of a dose, and the distance coveredby the trigger 3 during the delivery of a dose increases as the amountof drug which still has to be delivered to deliver the whole dose setdecreases. The distance covered by the trigger 3 during a delivery of adose may especially be proportional to the dose delivered.

The dose delivery is completed when the end-of-dose stop 36 is reachedand the mechanism is in the state shown in FIGS. 32 and 33. The movementof the trigger 3 covers an axial distance 52, which is larger the largerthe dose delivered and may particularly be proportional to the dosedelivered, if the threaded engagements are designed accordingly. Aproportionality between the axial distance 52 and the dose delivered canbe obtained by making the pitch of the thread 19 of the lead screw 9 andthe pitch of the first thread 34 of the number sleeve 11 both constant,for example. The sliding window 12 is at its proximal position anddisplays zero units remaining to be dispensed. The spring cap 18 is atits distal position, farthest away from the button 25, and the triggerspring 14 is compressed. The lead screw 9 is in a translated positioncorresponding to the translated position of the bung 5. Another dose cannow be set and delivered by the same operation as described above,except for the initial state according to FIGS. 19 and 20 beingsubstituted by the state of the mechanism according to FIGS. 32 and 33.

The mechanism can be used in any drug delivery device that is operatedto deliver a medicament from a receptacle like a cartridge, forinstance, in a number of doses that can be selected by a user. Thedevice is disposable and is not intended to be refilled. It ispreferably delivered to the user in a fully assembled condition readyfor use. The drug delivery device can be a pen-type device, for example,particularly a pen-type injector, which uses a needle to administer thedose that is dispensed.

The main spring 13 serves to store energy, which is charged as the userdials a dose and remains stored until the device is triggered fordispense by a shift of the trigger 3. Any dose size can be selected tosuit individual requirements, and the dialed number of predefined unitscan be displayed. The mechanism permits cancelling of a dose without anymedicament being dispensed by just reversing the dialing operation. Thetorque and force required to set and dispense a dose are independent ofthe force required to move the bung within the receptacle. The forcerequired to actuate the trigger 3 is small, providing a significantergonomic advantage, particularly for users with impaired dexterity. Themechanism can be designed in such a fashion that the trigger 3 moves byan axial distance 52 that is proportional to the volume of medicamentdispensed. Very clear tactile and visual feedback may be provided to theuser regarding the progress of dose delivery and thus allow them tocontrol the delivery very precisely. Furthermore the mechanism hasrelatively low part count and is consequently particularly attractivefor cost sensitive device applications.

1-15. (canceled)
 16. A mechanism for a drug delivery device, comprisinga body, a drive member movable in the body, a main spring that is loadedwhen a dose is set and is released for moving the drive member during adelivery of a dose, a movable trigger inhibiting a movement of the drivemember, a movement of the trigger releasing the main spring and thedrive member, characterized in that the trigger is moved from a startposition to an end position relative to the body during a setting of adose, the end position having a distance from the start position thatincreases as the dose set increases.
 17. The mechanism according toclaim 16, wherein the trigger is moved from the end position towards thestart position for a delivery of a dose.
 18. The mechanism according toclaim 16, wherein the end position of the trigger has a distance fromthe start position that depends on an amount of the dose set.
 19. Themechanism according to claim 18, wherein the distance covered by thetrigger comprises a portion that is proportional to the amount of thedose delivered.
 20. The mechanism according to claim 16, wherein thetrigger is axially movable with respect to and rotationally locked tothe body.
 21. The mechanism according to claim 16, further comprising: alocking feature releasably locking the drive member to the trigger, thelocking being released for drug delivery.
 22. The mechanism according toclaim 21, wherein the locking feature rotationally locks the drivemember to the trigger.
 23. The mechanism according to claim 22, furthercomprising: the locking feature comprising a spline of the trigger, anda spline of the drive member, the splines rotationally locking the drivemember to the trigger in such a way that the rotational locking isreleased by a movement of the trigger from the end position towards thestart position.
 24. The mechanism according to claim 21, furthercomprising: a trigger spring acting on the trigger, the trigger springtending to keep the drive member locked to the trigger.
 25. Themechanism according to claim 16, further comprising: an indicatormember, the drive member being unidirectionally rotationally coupled tothe indicator member.
 26. The mechanism according to claim 25, furthercomprising: a resilient element acting between the body and the drivemember, the resilient element being arranged to keep the drive membercoupled to the indicator member.
 27. The mechanism according to claim25, further comprising: a spring cap axially movable and rotationallylocked to the body, the main spring being fastened to the indicatormember and to the spring cap in such a manner that the main spring isloaded by a rotation of the indicator member relative to the spring cap.28. A drug delivery device comprising a mechanism according to claim 16.29. The drug delivery device of claim 28, wherein the drug deliverydevice is a pen-type device.
 30. The drug delivery device of claim 28,wherein the drug delivery device is a disposable device.